Pre-sterilized, single-use bag manifolds such as those used in bio-pharmaceutical production (see U.S. Pat. Nos. 6,712,963; 7,052,603 and 7,410,587, incorporated here by reference) lack the ability to monitor and validate important, analytical solution parameters during the processing of biopharmaceutical solutions. Such bag manifolds are used, for example, in preparative chromatography, tangential flow filtration (TFF), normal flow filtration (NFF), centrifugation or fluid transfer.
In-line, flow through-type sensors and detectors are well known in industry and are extensively used in analytical laboratories, pilot plants and production facilities. In-line conductivity detectors, in particular, are used in ion chromatography, preparative chromatography, flow injection analysis (FIA), tangential flow filtration (TFF), as well as water purity analysis. When these are intended for multiple use, typically made out of machined, stainless steel or plastic materials, they are intended for permanent installations and long-term use and are difficult to sterilize, require in-field calibration and validation by an experienced operator before use, and are very expensive, often costing thousands of dollars.
The use of a memory device imbedded in disposable clinical sensors has been reported. For example, U.S. Pat. No. 5,384,028 deals with the fabrication of an enzyme-based glucose biosensor that utilizes a sensor-imbedded data memory device and requires sensor calibration and/or validation by the clinician immediately prior to each use.
In-line sensors for use in bioprocessing applications must be designed to meet government regulations regarding device traceability and validation. In addition, in-line sensors must meet the application requirements for accuracy and precision. These requirements present extra challenges and pose unique problems when the in-line sensor is to be disposable and suitable for single use as desired. Another problem is how to provide disposable in-line sensors that are pre-calibrated. Also for aseptic sensor applications, each single-use sensor, must meet sterilization requirements. Furthermore, single-use sensors must meet economic requirements, i.e. sensors must be low cost, easy to replace with negligible disposal expense.
Meeting sensor sterilization requirements represents another very significant sensor design challenge. This is especially the case, when the sensor is intended for single-use bag manifold applications such as those referenced therein. The biotechnology and bio-pharmaceutical industries utilize four different sterilization methods: (1) autoclaving (i.e. timed exposure to pressurized steam at approximately 125° Celsius); (2) time-limited exposure to an ethylene oxide gas; (3) gamma ray irradiation up to 50 kGy; and (4) electron-beam irradiation.
For many single-use sensor applications, e.g. for bag manifolds, the preferred sterilization method by the industry is by gamma or electron-beam irradiation. The main advantage of gamma and electron-beam irradiation lies is that the entire, pre-assembled manifold, including bags, tubing, connectors and sensors, can be first sealed in a shipping bag or bags and then exposed to sterilizing radiation or electron-beam bombardment. The entire manifold assembly within the shipping bag system remains sterile for a rated period, unless compromised during shipment or storage.